Cholinergic Interneurons Amplify Thalamostriatal Excitation of Striatal Indirect Pathway Neurons in Parkinson's Disease Models

Asami Tanimura, Yijuan Du, Jyothisri Kondapalli, David L. Wokosin, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The motor symptoms of Parkinson's disease (PD) are thought to stem from an imbalance in the activity of striatal direct- and indirect-pathway spiny projection neurons (SPNs). Disease-induced alterations in the activity of networks controlling SPNs could contribute to this imbalance. One of these networks is anchored by the parafascicular nucleus (PFn) of the thalamus. To determine the role of the PFn in striatal PD pathophysiology, optogenetic, chemogenetic, and electrophysiological tools were used in ex vivo slices from transgenic mice with region-specific Cre recombinase expression. These studies revealed that in parkinsonian mice, the functional connectivity of PFn neurons with indirect pathway SPNs (iSPNs) was selectively enhanced by cholinergic interneurons acting through presynaptic nicotinic acetylcholine receptors (nAChRs) on PFn terminals. Attenuating this network adaptation by chemogenetic or genetic strategies alleviated motor-learning deficits in parkinsonian mice, pointing to a potential new therapeutic strategy for PD patients.

Original languageEnglish (US)
Pages (from-to)444-458.e6
JournalNeuron
Volume101
Issue number3
DOIs
StatePublished - Feb 6 2019

Keywords

  • Parkinson's disease
  • indirect pathway spiny projection neuron
  • motor learning
  • nicotinic acetylcholine receptor
  • parafascicular nucleus
  • presynaptic modulation
  • striatal cholinergic interneuron

ASJC Scopus subject areas

  • Neuroscience(all)

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